Critical
Apixaban × ritonavir
Direct oral anticoagulants (factor Xa inhibitors)×HIV protease inhibitor / pharmacokinetic booster
Mechanism
Ritonavir is the most potent CYP3A4 and P-glycoprotein inhibitor in clinical use (a pharmacokinetic booster in HIV regimens). Apixaban plasma levels roughly double. The FDA lists the combination as an absolute contraindication.
Symptoms
Gum bleeding, epistaxis, bruising without trauma, blood in urine or stool, menorrhagia. Severe cases include gastrointestinal or intracranial haemorrhage, gross haematuria with renal colic, spontaneous retroperitoneal haematomas. Symptoms may appear within days of co-prescription.
Management
The combination is not prescribed. For HIV patients on ritonavir-boosted regimens, anticoagulate with warfarin under INR control. Alternative: low molecular weight heparin for short courses.